 Magdalene So, PhD
Professor, Immunobiology
Director, Microbial Pathogenesis Program
Contact Information
Education
- PhD - University of Washington, 1976
Research:
TYPE IV PILI, MICROBES AND DISEASE
Microbes have evolved numerous mechanisms to adapt to, and co-exist with, their human host. Our goal is to define these mechanisms in molecular terms, and to understand how they influence the genesis of disease. We focus on two microbial pathogens, Neisseria gonorrhoeae and Neisseria meningitidis, and the role Type IV pili play in infection. We use cell biology, biochemistry and biophysics approaches to identify the bacteria-host interactions driven by Type IV pili, and the biological consequences that result from them. This information will allow us to identify new drug and vaccine targets and contribute to our general knowledge of microbial pathogenesis. Type IV pili are filamentous surface structures expressed by many pathogenic and free-living bacteria. The pilus fiber is a dynamic structure that undergoes cycles of extension, substrate tethering and retraction. Multiple pili on the same cell engaging in this process powers twitching motility (crawling over surfaces). Pilus retraction also enables bacteria to take up exogenous DNA (a form of genetic exchange), to engage in biofilm formation and quorum sensing, and, in the case of some pathogens, to attach to host cells. In the case of Neisseria, the physical force of pilus retraction transduced into the infected cell activates stress-responsive cascades, reorganizes host cell cortical structures, and dampens apoptosis signaling. These responses serve to promote infection with minimum damage to the host. |
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CLICK HERE to watch a movie of pilus retraction and read more about: Type IV pili Forces generated by retracting pili How epithelial cells respond to pilus retraction force Type IV pilus signaling through CD46 Commensal Neisseria Lab members and collaborators Lab publications and other reading material |
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Bacteria caught in the act of infecting a human cell
A cluster of Neisseria gonorrhoeae attached to a human epithelial cell. Bacteria are pseudocolored in yellow. All other features are in grey. The bacteria are covered by a network of fibers called Type IV pili. These Type IV pili extend from, and retract into, the body of the bacterium, much like a fishing line. When the fibers retract, they pull with tremendous force on the surface of a human cell, causing changes to the cell surface. Fiber retraction stimulates the formation of microvilli, seen here as thick tubes underneath and adjacent to the bacteria. It also causes the membrane to form “waves”. These and other changes to the human cell caused by Type IV pili are the beginning of the infection process. (D. Higashi and M. So, IMB/BIO5 Institute; A. Agellon, ARL; U of Arizona). |
Publications
Biomechanics/Dynamics
- Biais N, Ladoux B, Higashi DL, So M and Sheetz M. Cooperative retraction of bundled Type IV pili enables nanonewton force generation. PLoS Biol. 6:e87, 2008.
- Higashi DL, Lee SW, Snyder A, Weyand NJ, Bakke A and So M. Dynamics of Neisseria gonorrhoeae Attachment: Microcolony Development, Cortical Plaque Formation and Cytoprotection, Infect. Immun. 75:4743-4753, 2007.
Pilus retraction and host cell signaling
- Howie H, Shiflett and So M. ERK mediated downregulation of Bim and Bad during infection with N. gonorrhoeae. Infect Immun. 76:2715-2721, 2008.
- Weyand N, Lee SW, Higashi DL, Cawley D, Yoshihara P and So M. Monoclonal antibody detection of CD46 clustering beneath Neisseria gonorrhoeae microcolonies. Infect Immun. 74:2428-2435, 2006.
- Howie HL, Glogauer M and So M. N. gonorrhoeae Type IV pilus stimulates mechanosensitive pathways and cytoprotection through a pilT-dependent mechanism. PLoS Biol. 4:e100, 2005.
Peer-reviewed publications
Click here to see a listing of Peer-reviewed publications
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